A new view of the cortex, new insights into multiple sclerosis.

Abstract

Clinical–pathological correlations have been investigated using magnetic resonance‐based techniques in patients with multiple sclerosis arguably more intensively than for any other neurological disease. However, despite impressive accomplishments, consensus regarding a common pathology underlying clinical behaviours in patients with relapsing–remitting (RR), secondary progressive (SP) and primary progressive (PP) multiple sclerosis has been elusive. In part this may have been due to the singular focus on pathological changes in the white matter. Attention has been directed to the multifocal inflammatory lesions in white matter because their pathology appeared to offer an explanation for the characteristic RR course of the earlier stages of the disease in most patients. However, focal white matter lesions do not lead to disability progression in a simple way, particularly for PP multiple sclerosis, which is characterised by a relatively low white matter lesion load. White matter lesions alone also do not easily explain cognitive dysfunction in multiple sclerosis, evidence of which can be found in 40–65% of patients, including even a proportion of those presenting with otherwise apparently clinically isolated focal syndromes (Feinstein et al ., 1992). Pathological changes in grey matter provide an alternative basis for hypotheses concerning clinicopathological correlations in multiple sclerosis. Although recognised by early neuropathologists (Greenfield and King, 1936), the significance of inflammation and demyelination in grey matter was not widely appreciated. Recent histopathological studies have re‐examined grey matter involvement and suggest that the extent of pathology is potentially substantial (Peterson et al ., 2001; Cifelli et al ., 2002). In theory, a powerful approach to understanding the clinical significance of this pathology would be to follow changes in vivo , when they can be related directly with symptoms and signs. While magnetic resonance imaging is relatively insensitive to focal lesions in grey matter, it can measure grey matter volumes to high …